This K20 application is a proposal which would support the career development of the candidate as an investigator in the area of cocaine and alcohol abuse. This proposal focuses on the use of drug administration studies (which are referred to as pharmacological challenge studies) in human as a means of defining he psychophysiological and pharmacokinetics parameters of drugs of abuse and potential pharmacotherapeutic agents. One of the primary goals of the research plan includes the investigation of the psychophysiology of concurrent cocaine-alcohol consumption and determination of the contribution of cocaethylene, a metabolite formed by ethyl esterification of cocaine which appears to have pharmacological properties similar to cocaine, to observed effects. A second goal is to determine whether disulfiram is an effective pharmacologic challenge study to examine the effect of disulfiram on cocaine administration in human volunteers and a controlled outpatient study to determine the efficacy of disulfiram (or placebo) and psychotherapy for the treatment of cocaine-alcohol abuse. The proposed career development plan utilizes the expertise of several preceptors including Thomas Kosten, M.D. who will act as the primary preceptor and oversee the candidate's career development. Drs. Jatlow, Price, O'Malley and Fischmann will assist with development of the candidate's expertise in drug administration studies. Drs. Rounsaville and Schottenfeld will advise regarding clinical issues and clinical trials. Dr. McGlashan will act as a resource an clinical advisor for studies ongoing at the candidate primary location, the Yale Psychiatric Institute. Formal instruction needed to enhance the candidate's expertise in pharmacology and statistics is proposed to strengthen the ability to conduct sound research in this area. Participation in formal didactic seminars at Yale and presentation at scientific meeting is also proposed, as is continued participation by he candidate in teaching of trainees in the area of cocaine-alcohol abuse. These activities will contribute to the candidate's development as both a researcher and academician.